Biomimetic Design and Construction of an Artificial Lung

人工肺的仿生设计与构造

• 批准号: 8197702
• 负责人: Jeffrey T. Borenstein
• 金额: $ 30.58万
• 依托单位: CHARLES STARK DRAPER LABORATORY
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-12-01 至 2013-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8197702
• 关键词: Acute; Acute Lung Injury; Address; Adult Respiratory Distress Syndrome; Adverse event; Anticoagulation; Architecture; Artificial Respiration; Biomedical Engineering; Biomimetics; Blood; Blood Vessels; Blood Volume; Blood flow; Cardiopulmonary; Cause of Death; Chronic; Chronic Disease; Chronic Obstructive Airway Disease; Chronic lung disease; Clinical; Coagulation Process; Development; Devices; Disease; Elements; Failure; Future; Gases; Goals; Heart Diseases; Home environment; Human; Hypoxia; Infection; Injury; Lead; Left; Life; Lung; Lung Transplantation; Malignant Neoplasms; Mechanical ventilation; Medical Device; Membrane; Membrane Oxygenators; Microfabrication; Microfluidics; Organ; Organ Donor; Oxygen Therapy Care; Patients; Performance; Permeability; Physiology; Property; Research; Research Project Grants; Role; Saline; Solutions; Structure; Structure of parenchyma of lung; Surface; System; Technology; United States; Whole Blood; artificial lung; base; design; design and construction; improved; in vitro testing; lung basal segment; mortality; new technology; polydimethylsiloxane; respiratory assist; shear stress; technology development; three dimensional structure

The ultimate goal of this project is to develop artificial lung assist device technology to treat acute and chronic pulmonary failure. Chronic lung disease is the third-leading cause of death in the United States, exceeded only by heart disease and cancer. Currently there are no long-term solutions for chronic diseases such as Chronic Obstructive Pulmonary Disease (COPD) other than lung transplantation, and a severe shortage of donor organs limits this approach, leaving most patients relying on home oxygen therapy. For acute illnesses such as Adult Respiratory Distress Syndrome (ARDS), mechanical ventilation is typically required, and complications and mortality remain very high. Alternatives such as ExtraCorporeal Membrane Oxygenator (ECMO) therapy can only be used for a limited duration, require high levels of anticoagulation and involve numerous operational complexities. There is an urgent need for technological advances in artificial lung devices, including simplification and extended use of devices, a reduced need for anticoagulation, and high gas transfer rates in a compact format with low blood volumes. Here we propose an Exploratory Bioengineering Research Grant to pursue the development of technology for a bioartificial lung, based on biomimetic design principles and microfabrication technology to build scalable respiratory assist architectures capable of high levels of gas transport in a small and compact structure. Successful development of a bioartificial lung will require several critical elements, many of which have not been realized because of difficulties in mimicking natural lung physiology due to limitations in fabrication technology. The specific aims of this proposal are directed towards these elements, including the ability to design a biomimetic structure with small priming volume and high levels of gas permeability, and the establishment of an endothelialized microvascular network to support smooth blood flow without clotting in the absence of anticoagulative agents. These goals are consistent with future clinical targets including the ability to provide patients with long-term functional respiratory assist devices that do not require extensive anticoagulation and that can be enabled in a wearable or potentially implantable format. To accomplish these goals, we aim 1) To generate a biomimetic design and utilize microfabrication technology to construct an artificial lung module comprising microvascular networks and gas-permeable membranes, and 2) To establish endothelialized microfluidic network in vascular chamber and determine gas transport and blood flow coagulation properties of bioartificial lung construct.

该项目的最终目标是开发人工肺辅助装置技术来治疗急慢性疾病 肺衰竭。慢性肺病是美国第三大死因，超过 仅由心脏病和癌症引起。目前对于慢性病如慢性病尚无长期解决方案。 肺移植以外的慢性阻塞性肺疾病（COPD），以及严重缺乏 捐赠器官限制了这种方法，使得大多数患者只能依靠家庭氧疗。对于急性疾病 例如成人呼吸窘迫综合征 (ARDS)，通常需要机械通气，并且 并发症和死亡率仍然很高。替代品如体外膜氧合器 (ECMO) 疗法只能在有限的时间内使用，需要高水平的抗凝治疗并涉及 许多操作复杂性。人工肺亟待技术进步 设备，包括设备的简化和扩展使用、抗凝需求的减少以及高 紧凑形式的气体传输速率和低血容量。在这里我们提出一个探索性的 生物工程研究补助金，用于开发基于生物人工肺的技术 仿生设计原理和微加工技术构建可扩展的呼吸辅助架构 能够在小而紧凑的结构中进行高水平的气体传输。成功开发了一个 生物人工肺需要几个关键要素，其中许多要素尚未实现，因为 由于制造技术的限制，模仿自然肺生理学很困难。具体目标 该提案的目的是针对这些要素，包括设计仿生结构的能力 小的启动体积和高水平的气体渗透性，以及内皮化的建立 微血管网络可在没有抗凝剂的情况下支持顺畅的血流而不发生凝血。 这些目标与未来的临床目标一致，包括为患者提供长期治疗的能力 功能性呼吸辅助装置，不需要大量抗凝，并且可以在 可穿戴或可能植入的形式。为了实现这些目标，我们的目标是 1) 产生仿生 设计并利用微加工技术构建包含微血管的人工肺模块 网络和透气膜，2）在血管中建立内皮化微流体网络 室并确定生物人工肺构造的气体运输和血流凝固特性。

项目成果

Performance and scaling effects in a multilayer microfluidic extracorporeal lung oxygenation device.

• DOI: 10.1039/c2lc21156d
• 发表时间: 2012-05-07
• 期刊: Lab on a chip
• 影响因子: 6.1
• 作者: Kniazeva T;Epshteyn AA;Hsiao JC;Kim ES;Kolachalama VB;Charest JL;Borenstein JT
• 通讯作者: Borenstein JT